title: Curcumin protects the developing lung against long-term hyperoxic injury.
abstract: Curcumin, a potent anti-inflammatory and antioxidant agent, modulates peroxisome proliferator-activated receptor-γ signaling, a key molecule in the etiology of bronchopulmonary dysplasia (BPD). We have previously shown curcumin's acute protection against neonatal hyperoxia-induced lung injury. However, its longer-term protection against BPD is not known. Hypothesizing that concurrent treatment with curcumin protects the developing lung against hyperoxia-induced lung injury long-term, we determined if curcumin protects against hyperoxic neonatal rat lung injury for the first 5 days of life, as determined at postnatal day (PND) 21. One-day-old rat pups were exposed to either 21 or 95% O₂ for 5 days with or without curcumin treatment (5 mg/kg) administered intraperitoneally one time daily, following which the pups grew up to PND21 in room air. At PND21 lung development was determined, including gross and cellular structural and functional effects, and molecular mediators of inflammatory injury. To gain mechanistic insights, embryonic day 19 fetal rat lung fibroblasts were examined for markers of apoptosis and MAP kinase activation following in vitro exposure to hyperoxia for 24 h in the presence or absence of curcumin (5 μM). Curcumin effectively blocked hyperoxia-induced lung injury based on systematic analysis of markers for lung injury (apoptosis, Bcl-2/Bax, collagen III, fibronectin, vimentin, calponin, and elastin-related genes) and lung morphology (radial alveolar count and alveolar septal thickness). Mechanistically, curcumin prevented the hyperoxia-induced increases in cleaved caspase-3 and the phosphorylation of Erk1/2. Molecular effects of curcumin, both structural and cytoprotective, suggest that its actions against hyperoxia-induced lung injury are mediated via Erk1/2 activation and that it is a potential intervention against BPD.
authors.affiliation: Dept. of Pediatrics, Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, David Geffen School of Medicine at UCLA, 1124 West Carson St., Torrance, CA 90502. vrehan@labiomed.org.
authors.forename: R
authors.initials: R
authors.lastname: Sakurai
authors.forename: P
authors.initials: P
authors.lastname: Villarreal
authors.forename: S
authors.initials: S
authors.lastname: Husain
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Sakurai
authors.forename: E
authors.initials: E
authors.lastname: Tou
authors.forename: J S
authors.initials: JS
authors.lastname: Torday
authors.forename: V K
authors.initials: VK
authors.lastname: Rehan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D018496:Hyperoxia / Q000188:drug therapy* / Q000196:embryology / Q000235:genetics / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005353:Fibronectins; D020011:Protective Agents; D016212:Transforming Growth Factor beta; D014280:Triglycerides; D004549:Elastin; D003474:Curcumin
keywords: apoptosis; brochopulmonary dysplasia; curcumin; hyperoxia; inflammation